A very low protein diet could help in the treatment of colon cancer

A specific therapeutic diet can help in the adjunctive treatment of colon cancer. Research conducted at the University of Michigan Rogel Cancer Center proves that a diet with minimal protein can increase the effectiveness of chemotherapy by making cancer cells more vulnerable. The study has been published in the journal Gastroenterology.

According to the researchers, the very low protein diet blocks the signaling pathways that the cancer uses to feed itself. Cancer cells need nutrients to survive and grow. One of the most important nutrient sensing molecules in a cancer cell is called mTORC1, often called the “master regulator of cell growth.” This cell allows cells to sense different nutrients and therefore grow and proliferate. When nutrients are limited, cells reduce the nutrient sensing cascade and “turn off” mTORC1.

What is the most appropriate diet for colon cancer?

mTORC1 is known to be overactive in colon cancer, but the key question was whether colon tumors hijack nutrient-sensing pathways to activate the master regulator. However, the study has verified that “in colon cancer, when available nutrients are reduced, cells don’t know what to do. Without the nutrients to grow, they go through a kind of crisis that leads to massive cell death,” explains lead author Yatrik M. Shah, a professor of physiology at Michigan Medical School.

The regulator, mTORC1, controls how cells use nutritional signals to grow and multiply. It is very active in cancers with certain mutations and is known to promote cancer resistance to standard treatments. A diet low in protein, and specifically a reduction in two key amino acids, is capable of modifying nutritional signals through a complex called GATOR.

GATOR1 and GATOR2 work together to keep mTORC1 active. When a cell has a lot of nutrients, GATOR2 activates mTORC1. When nutrients are low, GATOR1 turns off mTORC1. The scientific finding is that limiting the intake of certain amino acids can specifically block this nutrient signaling pathway.

Previous efforts to block mTORC had focused on inhibiting cancer-causing signals. But the inhibitors used caused significant side effects, and when patients stopped taking them, the cancer returned. The study suggests that blocking the nutrient pathway by limiting amino acids through a low protein diet offers an alternative and much safer way to block the mTORC pathway.

“We knew that nutrients were important in regulating mTORC, but we didn’t know how they directly signal mTORC. We found that the nutrient signaling pathway is just as important in regulating mTORC as the oncogenic signaling pathway,” explains the first author of the study, Sumeet Solanki, Ph.D., a researcher at the Rogel Cancer Center.

Diet increases the effectiveness of chemotherapy and radiation therapy

the researchers confirmed their findings in cells and mice, where they saw that limiting amino acids stopped cancer growth and led to increased cell death. They also looked at tissue biopsies from colon cancer patients, where it was confirmed that high mTORC markers correlated with increased resistance to chemotherapy.

“A low-protein diet will not be a stand-alone treatment, but it can be combined with chemotherapy,” Solanki said. But putting cancer patients on a protein-deficient diet long-term isn’t ideal, because they often experience muscle weakness and weight loss. But if you can find key windows, such as at the start of chemotherapy or radiotherapy, where patients could follow a low-protein diet for a week or two, the efficacy of the treatments could potentially be increased.

Future research will delve into the therapeutic windows in which it is more effective to limit amino acids. The researchers will also seek to understand how these pathways create resistance to treatment and whether an inhibitor could block the GATOR complexes.

Scientific reference: